Upregulation of ROBO3 promotes proliferation, migration and adhesion of AML cells and affects the survival of AML patients.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, which is the most common and severe acute leukemia in adults. Its occurrence, development and prognosis are affected by many factors, and more research is still needed to further guide its treatment. Here, we found that roundabout3 (ROBO3) was associated with poor prognosis in AML through bioinformatics analysis. We then found that overexpression of ROBO3 promoted AML cell proliferation, adhesion and migration while knockdown of ROBO3 had opposite effects. We subsequently found that ROBO3 regulated CD34 expression in AML cells, and this regulatory effect may be achieved through the Hippo-YAP pathway. The inhibitors of this pathway, K-975 and verteporfin, showed an inhibitory effect on AML cells with high ROBO3 expression. ROBO3 was also found to be significantly increased in bone marrow samples from AML patients. Our research indicates that ROBO3 plays an important role in the development of AML, which suggests that ROBO3 can be a prognostic biomarker and potential therapeutic target for AML.

Sclerostin antibody promotes bone formation through the Wnt/ß-catenin signaling pathway in femoral trochlear after patellar instability.

PURPOSE: The molecular mechanism of patellar instability (PI) remains unknown. The purpose of this study was to explore the function of SOST/sclerostin in PI and examine the effect of sclerostin antibody (Scl-Ab). MATERIALS AND METHODS: We randomly divided 60 male 3-week-old C57Bl/6 mice into four groups: sham, PI, Scl-Ab intraperitoneal injection (Scl-Ab IP), Scl-Ab intraarticular injection (Scl-Ab IA). PI was established in the latter three groups. The Scl-Ab IP/IA groups were administered with an intraperitoneal/intraarticular Scl-Ab injection (100 mg/kg, 20 µl), respectively, at 5-day intervals. Distal femurs were collected 30 days after the surgery. The SOST/sclerostin, ß-catenin, ALP, OPG and RANKL expression in distal femur were determined. Trochlear morphology and structural parameters of the trabecular and cortical bone compartments were determined by micro-CT. Further sub-regional analysis was performed. HE staining and Masson's trichrome staining were performed to evaluate cartilage changes. RESULTS: PI increased the expression of SOST/sclerostin and RANKL, and decreased ß-catenin, ALP and OPG levels, while Scl-Ab IP reversed these changes. Scl-Ab IP brought trochlear morphology closer to normality. Additionally, Scl-Ab IP significantly improved most of the bone parameters. Importantly, both PI and Scl-Ab IP acted mainly on trabecular bone. Histological analysis showed that Scl-Ab IP protected cartilage from degeneration. However, Scl-Ab IA did not protect against bone loss or cartilage degradation. CONCLUSIONS: SOST/sclerostin plays an important role in PI and systemic Scl-Ab use promotes bone formation through the Wnt/ß-catenin signaling pathway in the femoral trochlear after PI.

Isolated medial patellofemoral ligament reconstruction is valid to stabilize patellofemoral joint but uncertain to reduce patellar height in setting of lateral patellar dislocation and patella alta.

INTRODUCTION: Medial patellofemoral ligament reconstruction (MPFLR) is the most commonly used surgical treatment for patients with lateral patellar dislocation (LPD). It is still poorly understood whether or not MPFLR has a contributory effect on decreasing patellar height. MATERIALS AND METHODS: Forty-five patients who underwent isolated MPFLR for LPD and patella alta were evaluated with a mean follow-up period of 24 months (22-25 months). Knee joint functions were evaluated by Banff patellofemoral instability instrument (BPII) 2.0 scores and Kujala scores. Patellofemoral engagement and stability were assessed by the patella tilt angle (PTA) and patellar congruence angle (PCA) measured by CT scans, and the patellar-glide test. Patellar height was calculated on lateral radiographs according to three methods: Caton-Deschamps ratios (CDR), Insall-Salvati ratios (ISR), and Blackburne-Peel ratios (BPR). A threshold value of p < 0.05 denoted a statistically significant difference. RESULTS: Significant improvements were found in both BPII 2.0 scores, which increased from 41.7 to 77.8 (p < 0.001) and Kujala scores, which increased from 49.2 to 85.5 (p < 0.001). Post-operative PTAs and PCA decreased from 19.6 ± 8.8 to - 3.4 ± 6.2, and from 24.6 ± 7.3 to 13.1 ± 3.8 degrees respectively (p < 0.001). No patients showed lateral translation more than grade II in the patellar-glide test. Regarding patellar height, a tiny reduction (Δ = 0.02, Δ max = 0.09) was discovered in using CDR (p = 0.027), rather than ISR or BPR. All measurements of radiographic indices had an excellent intra- and inter-rater reliability (ICC > 0.75). CONCLUSIONS: Isolated anatomic MPFLR is sufficient to achieve good clinical outcomes, as well as patellofemoral stability and high rates of return-to-sport. However, it is unclear if the reconstructed MPFL has a contributory effect on reducing patellar height.

Emergency tracheal intubation peri-operative risk factors and prognostic impact after esophagectomy.

BACKGROUND: Emergent endotracheal intubation (ETI) is a serious complication after Oesophagectomy. It is still unclear that perioperative risk factors and prognosis of these patients with ETI. METHODS: Between January 2015 and December 2018, 21 patients who received ETI after esophagectomy were enrolled (ETI group) at the department of thoracic surgery, Fujian Union hospital, China. Each study subject matched one patient who underwent the same surgery in the current era were included (control group). Patient characteristics and perioperative factors were collected. RESULTS: Patients with ETI were older than those without ETI (p = 0.022). The patients with history of smoking in ETI group were significantly more than those in control group (p = 0.013). The stay-time of postanesthesia care unit (PACU) in ETI group was significantly longer than that in control group (p = 0.001). The incidence of anastomotic leak or electrolyte disorder in ETI group was also higher than that in control group (p = 0.014; p = 0.002). Logistic regression analysis indicated history of smoke (HR 6.43, 95%CI 1.39-29.76, p = 0.017) and longer stay time of PACU (HR 1.04, 95%CI 1.01-1.83, p = 0.020) both were independently associated with higher risks of ETI. The 3-year overall survival (OS) rates were 47.6% in patients with ETI and 85.7% in patients without ETI (HR 4.72, 95%CI 1.31-17.00, p = 0.018). COX regression analysis indicated ETI was an independent risk factor affecting the OS. CONCLUSION: The study indicated that history of smoking and longer stay-time in PACU both were independently associated with higher risks of ETI; and ETI was an independent risk factor affecting the OS of patients after esophagectomy. TRIAL REGISTRATION: This trial was retrospectively registered with the registration number of ChiCTR2000038549.

A Smart "Sense-and-Treat" Nanoplatform Based on Semiconducting Polymer Nanoparticles for Precise Photothermal-Photodynamic Combined Therapy.

Integrated theranostic nanoplatforms with biomarker recognition and photothermal- and photodynamic (PTT/PDT) therapy is in high demand but remains challenging. Herein, a "sense-and-treat" nanoplatform based on semiconducting polymer nanoparticles (SPNs) for ratiometric bioimaging of phospholipase D (PLD) activity and PTT/PDT combined therapy was proposed. Semiconducting polymer nanoparticles (PSBTBT NPs) serve not only as photothermal agents but also as fluorescent quenchers of Rhodamine B (Rhod B) through a PLD-cleavable linker. Chlorin e6 (Ce6) was used as a photodynamic agent and fluorescence reference. The obtained nanoplatform (PSBTBT-Ce6@Rhod NPs) showed high PDT efficiency and photothermal performance upon single laser irradiation. The PTT/PDT combined therapy achieved more efficient tumor inhibition results as compared with single treatments. In addition, the overexpressed biomarker PLD in tumor tissue will cleave Rhod, leading to the fluorescence recovery of Rhod B and thus allowing the activatable fluorescence imaging of tumor and targeted phototherapy.

Emergency tracheal intubation during off-hours is not associated with increased mortality in hospitalized patients: a retrospective cohort study.

BACKGROUND: The prognosis of hospitalized patients after emergent endotracheal intubation (ETI) remains poor. Our aim was to evaluate the 30-d hospitalization mortality of subjects undergoing ETI during daytime or off-hours and to analyze the possible risk factors affecting mortality. METHODS: A single-center retrospective study was performed at a university teaching facility from January 2015 to December 2018. All adult inpatients who received ETI in the general ward were included. Information on patient demographics, vital signs, ICU (Intensive care unit) admission, intubation time (daytime or off-hours), the department in which ETI was performed (surgical ward or medical ward), intubation reasons, and 30-d hospitalization mortality after ETI were obtained from a database. RESULTS: Over a four-year period, 558 subjects were analyzed. There were more male than female in both groups (115 [70.1%] vs 275 [69.8%]; P = 0.939). A total of 394 (70.6%) patients received ETI during off-hours. The patients who received ETI during the daytime were older than those who received ETI during off-hours (64.95 ± 17.54 vs 61.55 ± 17.49; P = 0.037). The BMI of patients who received ETI during the daytime was also higher than that of patients who received ETI during off-hours (23.08 ± 3.38 vs 21.97 ± 3.25; P < 0.001). The 30-d mortality after ETI was 66.8% (373), which included 68.0% (268) during off-hours and 64.0% (105) during the daytime (P = 0.361). Multivariate Cox regression analysis found that the significant factors for the risk of death within 30 days included ICU admission (HR 0.312, 0.176-0.554) and the department in which ETI was performed (HR 0.401, 0.247-0.653). CONCLUSIONS: The 30-d hospitalization mortality after ETI was 66.8%, and off-hours presentation was not significantly associated with mortality. ICU admission and ETI performed in the surgical ward were significant factors for decreasing the risk of death within 30 days. TRIAL REGISTRATION: This trial was retrospectively registered with the registration number of ChiCTR2000038549 .

Spectral response characteristics of the transmission-mode aluminum gallium nitride photocathode with varying aluminum composition.

In order to research spectral response characteristics of transmission-mode nanostructure aluminum gallium nitride (AlGaN) photocathodes, the AlGaN photocathodes materials with varied aluminum (Al) composition were grown by metalorganic chemical vapor deposition (MOCVD) and its optical properties were measured. The Al compositions of each AlGaN film of the photocathodes were analyzed from their adsorption properties curves; their thickness was also calculated by the matrix formula of thin-film optics. The nanostructure AlGaN photocathodes were activated with the Caesium-Oxygen (Cs-O) alternation, and after the photocathode was packaged in vacuum, their spectrum responses were measured. The experimental results showed that the trend of spectrum response curves first increased and then decreased along with the increasing of the incident light wavelength. The peak spectrum response value was 17.5 mA/W at 255 nm, and its quantum efficiency was 8.5%. The lattice defects near the interface of the AlGaN heterostructure could impede the electron motion crossing this region and moving toward the photocathode surface; this was a factor that reduces the electron emission performance of the photocathodes. Also, the experimental result showed that the thickness of each AlGaN layer affected the electron diffusion characteristics; this was a key factor that influenced the spectrum response performance.

Current spectral norm and phase variation based fault region identification for active distribution network.

The paper presents a fault region identification method for the active distribution network (ADN) with limited PMU. First, PMU configuration and region division strategies are proposed based on the network topology. Next, the difference in three-phase current variations between the normal and fault regions of the ADN is analyzed. A multi-dimensional state monitoring matrix is built using the measured current data. The spectral norm ratio coefficient is constructed based on the 2-norm to lower the complexity of the multi-dimensional state monitoring matrix and quantify the difference in state changes before and after the fault occurs in each region. Then, the fault region is identified by combining each region's spectral norm ratio coefficient and the change of the current phase. Finally, an IEEE 33-node simulation model is created to simulate faults under different working conditions. According to the simulation results, the suggested approach is less impacted by fault type, neutral point grounding mode, and transition resistance. Furthermore, even if the communication does not match the rigorous synchronization requirements, the proposed method can still complete the fault identification of the distribution network correctly and has high robustness.

Intravenous application of human umbilical cord mesenchymal stem cells alleviate neuropathic pain by suppressing microglia activation in rats.

Objective: Neuropathic pain has been considered as one of the most serious chronic pain subtypes and causes intolerable suffering to patients physically and mentally. This study aimed to verify the analgesic effect of intravenous administration of human umbilical cord mesenchymal stem cells (HUC-MSCs) upon rats with chronic constriction injury (CCI)-induced neuropathic pain and the concomitant mechanism via modulating microglia. Methods: 30 male SD rats were randomized divided into three groups (n = 10 per group): Sham + Saline group (S&S group), CCI + Saline group (C&S group) and CCI + HUC-MSCs group (C&U group). Rats were injected with either saline or HUC-MSCs via the caudal vein on the 7th day after modelling. The paw mechanical withdrawal threshold (PMWT) and thermal withdrawal latency (TWL) of the ligation side were measured before (day 0) and after (day 1, 3, 5, 7, 9, 11, 13, and 15) modelling. On day 15 after modelling, western-blotting and immunofluorescent staining were used to assess the expressive abundance of Iba-1 (a typical biomarker of activated microglia) in the ligation side of the spinal cord dorsal horn, and ultrastructural changes of the ligation of sciatic nerve were evaluated by transmission electron microscope (TEM). Results: Compared with the S&S group, PMWT and TWL in the C&S group were significantly decreased on day 5 and then persisted to day 15 after modelling (C&S vs S&S, P < 0.05), while a significant amelioration of mechanical hyperalgesia (day 13, day 15) and thermal allodynia (day 9, day 11, day 15) was observed in the C&U group (C&U vs C&S, P < 0.05). Meanwhile, the expression of Iba-1 was significantly suppressed by systemic infusion of HUC-MSCs in the C&U group according to western-blotting and immunofluorescent staining analyses (P < 0.05). With the aid of TEM detection, we intuitively noticed the efficacious reconstruction of the laminate structure of the sciatic nerve ligation, elimination of mitochondrial swelling, and formation of new myelination were noted on day 15 after modelling in the C&U group. Conclusions: Overall, intravenous administration of HUC-MSCs systemically revealed an ameliorative effect upon CCI-induced neuropathic pain in SD rats by inhibiting microglia activation in the dorsal horn of the impaired spinal cord and alleviating sciatic nerve injury. Our findings supply new references for the further development of HUC-MSCs-based cytotherapy for neuropathic pain administration.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial.

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2, which results in blindness in the working-age population, and there is currently no available treatment. Here, we report the results of the first-in-human clinical trial (NCT04722107) of gene therapy for Bietti crystalline corneoretinal dystrophy, including 12 participants who were followed up for 180-365 days. This open-label, single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein (rAAV2/8-hCYP4V2). Participants received a single unilateral subretinal injection of 7.5 × 1010 vector genomes of rAAV2/8-hCYP4V2. Overall, 73 treatment-emergent adverse events were reported, with the majority (98.6%) being of mild or moderate intensity and considered to be procedure- or corticosteroid-related; no treatment-related serious adverse events or local/systemic immune toxicities were observed. Compared with that measured at baseline, 77.8% of the treated eyes showed improvement in best-corrected visual acuity (BCVA) on day 180, with a mean ± standard deviation increase of 9.0 ± 10.8 letters in the 9 eyes analyzed (p = 0.021). By day 365, 80% of the treated eyes showed an increase in BCVA, with a mean increase of 11.0 ± 10.6 letters in the 5 eyes assessed (p = 0.125). Importantly, the patients' improvement observed using multifocal electroretinogram, microperimetry, and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment. We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2 (named ZVS101e).

[Anesthetic management of elderly patients during percutaneous endoscopic gastrostomy].

OBJECTIVE: To evaluate anesthetic techniques for elderly patients during percutaneous endoscopic gastrostomy (PEG). METHODS: Clinical data about 5 cases aged 80 years or more undergoing PEG from June 2012 to May 2013 in Chinese People's Liberation Army General Hospital were retrospectively analyzed and literature review. RESULTS: Analgesia/minimal sedation combined with local anesthesia (LA including throat spray and operative site infiltrated ) is employed in the one of patients with Tracheoesophageal Fistula (TEF), for the remaining patients, analgesia/deep sedation and LA combination were used, during induction, temporary respiratory depression, blood pressure and heart rate decreased occurred respectively in the different patient, assisted ventilation and ephedrine IV was effective, the anesthesia strategy was to maintain a desired sedation with propofol or etomidate intravenously in small increments or by adjusted infusion , and to keep SpO2 at 95% or more with a supplemental oxygen through face mask under spontaneous ventilation. During the therapeutic period, an increase in blood pressure (BP) and heart rate (HR), slight cough occurred in one patient. Of all cases undergoing this procedure uneventfully and recovering well at the end of surgery without aspiration, asthma or airway obstruction, 4 were placed with jejunal feeding tube successfully, the mean duration of surgery is 80 min, ranging between 40 and 150 min, no anesthesia-related or cardiorespiratory complications occurred at follow-up. CONCLUSIONS: a combination of intravenous sedative/analgesic anesthesia with LA is efficiently and safely suited to the patients at advanced age during PEG, for anesthesiologists, it should be the most important tenets of anesthetic practice to have preanesthetic evaluation well done about cardiorespiratory function and the ability of individual cooperation with anesthesia providers, to control airway and to manage circulatory system intraoperatively.

Anesthesia via peripheral nerve blocks during total knee replacement has no effect on postoperative inflammation in elderly patients.

BACKGROUND: We have previously shown that, compared with general anesthesia (GA), the procedure of peripheral nerve blocks (PNB) facilitates faster recovery of elderly patients from total knee replacement (TKR). Here, we investigated whether the faster recovery is associated with decreased perioperative stress and inflammation and decreased incidences of postoperative complications. METHODS: After randomization, 165 patients aged ≥65 years underwent TKR under GA or PNB. The primary outcomes were the perioperative inflammation and stress levels, based on the serum C-reactive protein and interleukin-6 levels, erythrocyte sedimentation rate, white-blood cell and neutrophil counts, and blood-sugar level. The secondary outcomes were the postoperative complications, including cardiovascular, respiratory, and hepatic or renal complications, insomnia, delirium, electrolyte disturbances, and nausea and vomiting. RESULTS: The two groups were not significantly demographically different (p > .05). Of the cytokines related to stress and inflammation, the differences of time points were statistically significant between the two groups (p < .01), but two-way ANOVA revealed no interaction between the time points and groups. Incidences of postoperative complications were far lower in PNB group than in GA group (p = .006). Incidences of postoperative respiratory complications (p = .005) and postoperative nausea and vomiting (p = .040) were significantly lower in PNB group than in GA group. There were no significant differences in other complications between the two groups (p > .05). CONCLUSIONS: PNB does not alleviate the stress and inflammation in elderly patients post TKR but significantly reduces the incidences of postoperative complications, especially respiratory complications, and nausea and vomiting. (ClinicalTrials.gov Identifier: NCT01871012).

Ultrasonic visualization technique for anatomical and functional analyses of the sciatic nerve in rats.

Background and objective: Ultrasound has been widely used in the diagnosis and minimally invasive treatment of peripheral nerve diseases in the clinic, but there is still a lack of feasibility analysis in rodent models of neurological disease. The purpose of this study was to investigate the changes in the cross-sectional area of the sciatic nerve of different genders and body weights and to explore the effectiveness and reliability of an ultrasound-guided block around the sciatic nerve in living rats. Methods: Using ultrasound imaging anatomy of the sciatic nerve of rats, the cross-sectional area of the sciatic nerve in rats of different genders from 6 to 10 weeks old was calculated, and then analyzed its correlation with body weight. Further analyses were conducted through behavioral and cadaveric studies to evaluate the feasibility of ultrasound-guided perineural injection of the sciatic nerve in rats. Results: We first reported that the sciatic nerve cross-sectional area of rats was increased with age (F = 89.169, P < 0.001), males had a higher sciatic nerve cross-sectional area than females (F = 60.770, P < 0.001), and there was a positive correlation with body weight (rMale = 0.8976, P < 0.001; rFemale = 0.7733, P < 0.001). Behavioral observation of rats showed that the lower extremity complete block rate was 80% following the administration of drugs around the sciatic nerve under ultrasound guidance and staining with methylene blue occurred in all sciatic nerves and surrounding muscles and fascia using 20 ultrasound-guided injections. Conclusions: Ultrasound visualization technology can be used as a new auxiliary evaluation and intervention therapy for animal models of peripheral nerve injury, and will provide overwhelming new references for the basic research of neurological diseases.

Mdivi-1 improves postoperative neurocognitive disorders in aged rats undergoing splenectomy by inhibiting dynamin-related protein-1.

Background: The regulatory role of mitochondria in the inflammatory response of the nervous system postoperatively remains unclear. This study explored the relationship between mitochondria and postoperative neurocognitive dysfunction (PNCD) by regulating mitochondrial function in aged rats undergoing splenectomy. Methods: A total of 120 aged rats were randomly divided into five groups (n=24) as follows: Control group (not subjected to any form of treatment), Sham group (subjected only to sham-splenectomized operation after anesthesia), Splenectomy group (only underwent splenectomy after anesthesia), Synonyms Mitochondrial division inhibitor 1 (Mdivi-1) group [treated with Mdivi-1, a dynamin-relatedprotein 1 (Drp1) inhibitor], and Dimethyl Sulfoxide (DMSO) group (treated with DMSO, a solvent). Inflammatory markers, namely interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNF-α), were measured in the plasma and brains of the rats. Cognitive function was assessed using the Morris water maze test. Results: During the perioperative period, the physiological parameters did not differ among the five groups (P>0.05). The results of the Morris water maze experiments showed that the memory of the rats was significantly impaired after splenectomy, which was alleviated by Mdivi-1 administration (P=0.04). Postoperatively, the proinflammatory cytokine levels in the serum and hippocampus tissue were upregulated, while Mdivi-1 administration reduced this increase. The electron microscopy and hematoxylin-eosin (HE) staining results indicated that the structure of neurons and mitochondria was minimally impaired in the Mdivi-1 group. Conclusions: Aged rats that underwent splenectomy exhibited significant postoperative cognitive impairments. The selective inhibitor of Drp1, Mdivi-1, exerted protective effects against PNCD by ameliorating mitochondrial dysfunction and reducing the inflammatory response.

Modified long-axis in-plane ultrasound-guided radial artery cannulation in adult patients: A randomized controlled trial.

INTRODUCTION: For adults with small radial arteries, ultrasound-guided radial artery cannulation remains challenging and the relevant data is currently lacking. The study aimed to test the hypothesis that modified long-axis in-plane ultrasound guidance (M-LAIP) would improve success rates of radial artery cannulation in this population. PATIENTS AND METHODS: This was a prospective, randomised, and controlled clinical study that enrolled 201 adult patients with diameters of the radial artery less than 2.2 mm. Patients were randomised to M-LAIP, short-axis out-of-plane (SAOP), or conventional palpation (C-P) group according to different approaches of radial artery cannulation (M-LAIP, SAOP, and C-P). Outcome measurements included the success rate, cannulation time, and cannulation-related adverse events. RESULTS: The cannulation success rate was significantly higher in the M-LAIP group than in the SAOP or C-P groups (first success rate: 80.3% vs. 53.8% or 33.8%; P < 0.001; total success rate: 93.9% vs. 78.5% or 50.8%; P < 0.001). Total cannulation time in the M-LAIP group was shorter than that in the SAOP group (P = 0.002) or the C-P group (P < 0.001). The rates of posterior wall puncture and haematoma in the M-LAIP group were lower than that in the SAOP group or C-P group (P < 0.008). CONCLUSION: The use of the M-LAIP approach significantly improved the success rate of radial artery cannulation, shortened procedure time, and lowered the rates of posterior wall puncture and haematoma in adults with radial artery diameters less than 2.2 mm, compared with that achieved by the SAOP or C-P approach.

RNA-seq based integrative analysis of potential crucial genes and pathways associated with patellar instability.

Patellar instability (PI) is a common knee injury in adolescents, but the crucial biomarkers and molecular mechanisms associated with it remain unclear. We established a PI mouse model and investigated PI-related changes in gene expression by RNA sequencing (RNA-seq). Differentially expressed gene (DEG) analysis and enrichment analysis were performed to identify crucial genes and pathways associated with PI. Subsequently, a protein-protein interaction, DEG-miRNA, DEG-transcription factors, and DEG-drug interaction networks were constructed to reveal hub genes, molecular mechanism, and potential drugs for PI. Finally, the reliability of the sequencing results was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Upon comparison with the control group, 69 genes were differently expressed in PI, including 17 upregulated and 52 downregulated ones. The DEGs were significantly enriched in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway and immune responses. The protein-protein interaction network identified ten PI-related hub genes, all of which are involved in the JAK/STAT signaling pathway or inflammation-related pathways. DEG-miRNA and DEG-transcription factor networks offered new insights for regulating DEGs post-transcriptionally. We also determined potential therapeutic drugs or molecular compounds that could restore dysregulated expression of DEGs via the DGIdb database. RT-qPCR results were consistent with the RNA-seq, confirming the reliability of the sequencing data. Immunohistochemistry results suggested that JAK1 and STAT3 expression was increased in PI. Our study explored the potential molecular mechanisms in PI, provided promising biomarkers and suggested a molecular basis for therapeutic targets for this condition.

Thrombolysis Combined Therapy Using CuS@SiO2-PEG/uPA Nanoparticles.

Massive hemorrhage caused by the uncontrolled release of thrombolysis drugs is a key issue of thrombolysis therapy in clinical practice. In this study, we report a near-infrared (NIR) light-triggered drug delivery system, i.e., CuS@mSiO2-PEG (CSP) nanoparticles, for the loading of a thrombolytic drug (urokinase plasminogen activators, uPA). CSP nanoparticles with the CuS nanoparticles as photothermal agents and mesoporous SiO2 for the loading of uPA were synthesized using a facile hydrothermal method. The CSP core-shell nanoparticles were demonstrated to possess excellent photothermal performance, exhibiting a photothermal conversion efficiency of up to 52.8%. Due to the mesoporous SiO2 coating, the CSP core-shell nanoparticles exhibited appropriate pore size, high pore volume, and large surface area; thus, they showed great potential to be used as drug carriers. Importantly, the release of uPA from CuS@mSiO2-PEG/uPA (CSPA) carriers can be promoted by the NIR laser irradiation. The drug loading content of uPA for the as-prepared NIR-triggered drug delivery system was calculated to be 8.2%, and the loading efficiency can be determined to be as high as 89.6%. Due to the excellent photothermal effect of CSP nanocarriers, the NIR-triggered drug delivery system can be used for infrared thermal imaging in vivo. The in vivo thrombolysis assessment demonstrated that the NIR-triggered drug delivery system showed excellent thrombolytic ability under the irradiation of an 808 nm laser, showing the combined therapy for thrombolysis. As far as we know, the CSPA core-shell nanoparticles used as NIR-triggered drug delivery systems for thrombolysis have not been reported.

Modified long-axis in-plane ultrasound technique versus conventional palpation technique for radial arterial cannulation: A prospective randomized controlled trial.

BACKGROUND: A low first-pass success rate of radial artery cannulation was obtained when using the conventional palpation technique (C-PT) or conventional ultrasound-guided techniques, we; therefore, evaluate the effect of a modified long-axis in-plane ultrasound technique (M-LAINUT) in guiding radial artery cannulation in adults. METHODS: We conducted a prospective, randomized and controlled clinical trial of 288 patients undergoing radial artery cannulation. Patients were randomized 1:1 to M-LAINUT or C-PT group at Fujian Medical University Union Hospital between 2017 and 2018. Radial artery cannulation was performed by 3 anesthesiologists with different experience. The outcome was the first and total radial artery cannulation success rates, the number of attempts and the cannulation time, and incidence of complications. RESULTS: Two hundred eighty-five patients were statistically analyzed. The success rate of first attempt was 91.6% in the M-LAINUT group (n = 143) and 57.7% in the C-PT group (n = 142; P < .001) (odds ratio, 7.9; 95% confidence interval, 4.0-15.7). The total success rate (≤5 minutes and ≤3 attempts) in the M-LAINUT group was 97.9%, compared to 84.5% in the palpation group (P < .001) (odds ratio, 8.5; 95% confidence interval, 2.5-29.2). The total cannulation time was shorter and the number of attempts was fewer in the M-LAINUT group than that in the C-PT group (P < .05). The incidence of hematoma in the C-PT group was 19.7%, which was significantly higher than the 2.8% in the M-LAINUT group (P < .001). CONCLUSIONS: Modified long-axis in-plane ultrasound-guided radial artery cannulation can increase the first and total radial artery cannulation success rates, reduce the number of attempts, and shorten the total cannulation time in adults.

Preconditioning with +Gz acceleration (head-to-foot inertial load) produces neuroprotection against transient focal cerebral ischemia in rats.

Ischemic preconditioning is considered to be the most robust endogenous neuroprotectant. However, the conventional ischemic preconditioning protocol is both invasive and impractical to apply. The aim of the present study was to evaluate whether preconditioning with +Gz centrifuge acceleration (head-to-foot inertial load) which could induce brief episodes of sublethal ischemia in brain had neuroprotection against focal cerebral ischemic injury. A total of 85 male Sprague-Dawley rats were randomly assigned to five groups (n = 17 in each). The 2 Gz, 4 Gz, 6 Gz and 8 Gz groups were subjected to 3 min exposures at +2 Gz, +4 Gz, +6 Gz and +8 Gz, respectively for consecutive three times in animal centrifuge, with a 30-min rest period between each centrifuge run. The control group had no exposure to +Gz acceleration. Twenty-four hours after the last pretreatment, 12 rats in each groups were subjected to focal cerebral ischemia for 120 min and the other five rats in each group were sacrificed to measure the expression of heat shock protein 70(HSP70) in hippocampus by Western blot analysis. The results indicated that the 6 Gz and 8 Gz groups showed smaller infarct volume and lower neurologic deficit scores than the control group. The expression of HSP70 was significantly increased in 6 Gz and 8 Gz groups than those in the control group. Therefore, preconditioning with +Gz acceleration produced delayed neuroprotection against focal cerebral ischemia and that the neuroprotection may be related to the induction of HSP70.

Association between regulator of telomere elongation helicase 1 polymorphism and susceptibility to glioma.

BACKGROUND: Glioma is the most devastating type of malignant brain tumors in adults. Genetic factors play important roles in the pathogenesis of glioma. In recent years, some studies found that there were significant association between regulator of telomere elongation helicase 1 rs6010620 polymorphism and glioma susceptibility, however, the results were controversial. The aim of this study was to obtain a more exact estimation of the association between regulator of telomere elongation helicase 1 rs6010620 polymorphism and glioma through a meta-analysis. METHODS: The meta-analysis included 19 published case-control studies involving 8541 cases and 14226 controls. The included papers were searched from PubMed and Embase database. Odds ratio (OR) with 95% confidence interval (95% CI) were used to evaluate the association of regulator of telomere elongation helicase 1 rs6010620 polymorphism with glioma. RESULTS: A significant association between regulator of telomere elongation helicase 1 rs6010620 polymorphism and glioma susceptibility was observed for GG vs. AA+AG (OR=1.28, 95% CI=1.14-1.43) and G vs. A (OR=1.07, 95% CI=1.03-1.10). Further subgroup analysis based on ethnicity showed similar results in Asians and Caucasians. In the subgroup analysis of source of control, a significant association between the G allele and glioma susceptibility were found in population-based group and hospital-based group. CONCLUSIONS: The meta-analysis suggested that regulator of telomere elongation helicase 1 rs6010620 polymorphism was a risk factor for glioma. And this study also suggested that rs6010620 GG genotype and G allele may be indicators for the risk of glioma.